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MIS-C Comparative Effectiveness Study (MISTIC)

Primary Purpose

Multisystem Inflammatory Syndrome-Children

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Infliximab
Anakinra
Methylprednisolone
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multisystem Inflammatory Syndrome-Children

Eligibility Criteria

undefined - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. An individual aged <21 years presenting with

    1. Fever (>38.0°C for ≥24 hours; may be by subjective report) AND

    2. Two or more of the following (from two different systems; e.g. one from cardiac and one from mucocutaneous):

      Cardiac

      • Hypotension
      • Shock
      • Arrhythmia
      • Tachycardia
      • Left ventricular ejection fraction <55%
      • Valvulitis
      • Coronary artery enlargement (LAD or RCA Z-score ≥ 2.5)
      • Pericardial effusion Gastrointestinal
      • Diarrhea
      • Nausea/vomiting
      • Significant abdominal pain Immunologic
      • Lymphadenopathy (unilateral cervical or diffuse) Mucocutaneous
      • Bilateral conjunctival injection
      • Extremity swelling or erythema
      • Rash
      • Lip erythema/Strawberry tongue Neurologic
      • Altered mental status
      • Focal neurological deficits
      • Headache
      • Meningismus
    3. Laboratory evidence of inflammation, including but not limited to, an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase (LDH), neutrophilia, lymphopenia or hypoalbuminemia AND
    4. No alternative plausible diagnoses based on clinical judgement AND
    5. Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or suspected COVID-19 exposure AND
    6. Parent or legal guardian (or self if at least 18 years old) able and willing to provide informed consent and subject willing and able to provide assent when appropriate.

Exclusion Criteria:

  1. Known immunodeficiency
  2. Pre-existing medical condition that precludes receiving one or more of the study medications (e.g. TB, drug allergy to study medication).

Sites / Locations

  • Rady Children's Hospital
  • Children's Hospital Michigan

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Infliximab

Methylprednisilone (steroids)

Anakinra

Arm Description

Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.

Methylprednisilone (steroids) will be administered as 2 mg/kg IV or orally divided every 12 hours. At the time of hospital discharge the patient will be given a steroid taper that will take at least 3 weeks to complete.

Anakinra will be administered at a dose of 8 mg/kg/day IV or SQ with 100 mg every 6 hours as the max dose. This is discontinued with a taper during the hospitalization over 2-4 days once a patient is stable with significantly improved clinical course and laboratory profile.

Outcomes

Primary Outcome Measures

Anti-inflammatory treatment regimen lowest rate of second randomization
To determine the anti-inflammatory treatment from first randomization that has the lowest rate of second randomization.

Secondary Outcome Measures

Anti-inflammatory treatment regimen decrease CRP from baseline
To determine the anti-inflammatory treatment regimen that results in the most rapid reduction by 50 percent in the CRP level compared to baseline (pre-IVIG).
Anti-inflammatory treatment regimen quickest return of left ventricular ejection fraction
To determine the anti-inflammatory treatment regimen that results in the most rapid return to a sustained left ventricular ejection fraction of at least 55 percent from the start of the IVIG infusion.
Anti-inflammatory treatment regimen fewest adverse events
To determine the anti-inflammatory treatment regimen that results in the fewest serious adverse events attributed to study drug.

Full Information

First Posted
May 13, 2021
Last Updated
May 12, 2023
Sponsor
University of California, San Diego
Collaborators
Children's Hospital of Michigan
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1. Study Identification

Unique Protocol Identification Number
NCT04898231
Brief Title
MIS-C Comparative Effectiveness Study
Acronym
MISTIC
Official Title
Multisystem Inflammatory Syndrome Therapies in Children (MISTIC) Comparative Effectiveness Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 22, 2020 (Actual)
Primary Completion Date
December 22, 2023 (Anticipated)
Study Completion Date
December 22, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
Collaborators
Children's Hospital of Michigan

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In March 2020, children exposed to the virus that causes the COVID-19 illness, SARS-CoV-2, presented with fever and significant inflammation about a month after exposure to the virus. Some children were sick enough to require care in the intensive care unit for what came to be known as Multisystem Inflammatory Syndrome-Children (MIS-C).The clinical presentation shared many features with Kawasaki disease (KD), a self-limited inflammation that can cause ballooning of the arteries of the heart. Thus, physicians reached for many of the therapies used to treat children with KD. Despite the surge of COVID-19 cases and children continuing to present with MIS-C, there are no data that guide the choice of therapy. Thus, the investigators have designed a study to determine which combination of therapies is most effective in helping children with MIS-C recover quickly.
Detailed Description
This study is a multi-site, randomized, pragmatic, comparative effectiveness study of children with MIS-C. The current standard of care is that all MIS-C patients are initially treated with IVIG and receive additional therapy if they are severely ill or do not improve clinically. This study design will randomize subjects who have received IVIG but clinically warrant further anti-inflammatory therapy to one of three treatment arms (infliximab, steroids or anakinra) and allow for re-randomization to one of the two remaining arms if clinically warranted.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multisystem Inflammatory Syndrome-Children

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This is a randomized trial of 3 treatment arms
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Infliximab
Arm Type
Active Comparator
Arm Description
Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.
Arm Title
Methylprednisilone (steroids)
Arm Type
Active Comparator
Arm Description
Methylprednisilone (steroids) will be administered as 2 mg/kg IV or orally divided every 12 hours. At the time of hospital discharge the patient will be given a steroid taper that will take at least 3 weeks to complete.
Arm Title
Anakinra
Arm Type
Active Comparator
Arm Description
Anakinra will be administered at a dose of 8 mg/kg/day IV or SQ with 100 mg every 6 hours as the max dose. This is discontinued with a taper during the hospitalization over 2-4 days once a patient is stable with significantly improved clinical course and laboratory profile.
Intervention Type
Drug
Intervention Name(s)
Infliximab
Other Intervention Name(s)
Remicade, Inflectra, Remsima
Intervention Description
Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.
Intervention Type
Drug
Intervention Name(s)
Anakinra
Other Intervention Name(s)
Kineret
Intervention Description
Anakinra will be administered at a dose of 8 mg/kg/day IV or SQ with 100 mg every 6 hours as the max dose. This is discontinued with a taper during the hospitalization over 2-4 days once a patient is stable with significantly improved clinical course and laboratory profile.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Other Intervention Name(s)
Steriods
Intervention Description
Methylprednisilone (steroids) will be administered as 2 mg/kg IV or orally divided every 12 hours. At the time of hospital discharge the patient will be given a steroid taper that will take at least 3 weeks to complete.
Primary Outcome Measure Information:
Title
Anti-inflammatory treatment regimen lowest rate of second randomization
Description
To determine the anti-inflammatory treatment from first randomization that has the lowest rate of second randomization.
Time Frame
1 week
Secondary Outcome Measure Information:
Title
Anti-inflammatory treatment regimen decrease CRP from baseline
Description
To determine the anti-inflammatory treatment regimen that results in the most rapid reduction by 50 percent in the CRP level compared to baseline (pre-IVIG).
Time Frame
6 weeks
Title
Anti-inflammatory treatment regimen quickest return of left ventricular ejection fraction
Description
To determine the anti-inflammatory treatment regimen that results in the most rapid return to a sustained left ventricular ejection fraction of at least 55 percent from the start of the IVIG infusion.
Time Frame
6 weeks
Title
Anti-inflammatory treatment regimen fewest adverse events
Description
To determine the anti-inflammatory treatment regimen that results in the fewest serious adverse events attributed to study drug.
Time Frame
6 weeks

10. Eligibility

Sex
All
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: An individual aged <21 years presenting with Fever (>38.0°C for ≥24 hours; may be by subjective report) AND Two or more of the following (from two different systems; e.g. one from cardiac and one from mucocutaneous): Cardiac Hypotension Shock Arrhythmia Tachycardia Left ventricular ejection fraction <55% Valvulitis Coronary artery enlargement (LAD or RCA Z-score ≥ 2.5) Pericardial effusion Gastrointestinal Diarrhea Nausea/vomiting Significant abdominal pain Immunologic Lymphadenopathy (unilateral cervical or diffuse) Mucocutaneous Bilateral conjunctival injection Extremity swelling or erythema Rash Lip erythema/Strawberry tongue Neurologic Altered mental status Focal neurological deficits Headache Meningismus Laboratory evidence of inflammation, including but not limited to, an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase (LDH), neutrophilia, lymphopenia or hypoalbuminemia AND No alternative plausible diagnoses based on clinical judgement AND Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or suspected COVID-19 exposure AND Parent or legal guardian (or self if at least 18 years old) able and willing to provide informed consent and subject willing and able to provide assent when appropriate. Exclusion Criteria: Known immunodeficiency Pre-existing medical condition that precludes receiving one or more of the study medications (e.g. TB, drug allergy to study medication).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adriana Tremoulet, MD, MAS
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rady Children's Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Children's Hospital Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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MIS-C Comparative Effectiveness Study

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